Somatostatin is a tetradecapeptide which regulates the secretion of a number of pituitary, pancreatic, and gastrointestinal hormones. Recent evidence indicates that the tetradecapeptide somatostatin is synthesized as part of a large precursor. The overall objectives of this proposal are to elucidate the structures of the biosynthetic precursors of somatostatins found in anglerfish pancreatic islets and rat medullary thyroid carcinoma, to determine the structures of the rat and human somatostatin genes, to characterize the steps involved in precursor cleavage, glycosylation, and translocation within the somatostatin synthesizing cell, to determine the effects of regulatory factors on production of somatostatin mRNA in brain production in developing brain. To accomplish these aims, I will use the cloned anglerfish and rat somatostatin cDNAs which I have previously constructed to identify and sequence related precursors in cloned cDNA and genomic libraries. I will additionally use the cloned anglerfish and rat cDNAs to isolate somatostatin mRNA for studies of regulation of biosynthesis and post-translational processing. Finally, I will raise antibodies to a synthetic peptide corresponding to a portion of the amino-terminal extension of rat somatostatin whose sequence was deduced from the nucleotide sequence of the rat cDNA. An understanding at the molecular level of the events involved in somatostatin biosynthesis and secretion would have implications on nearly all aspects of endocrine physiology and may provide therapeutic approaches towards remedying abnormalities in pituitary, pancreatic, gastrointestinal, or neuronal function.